Macrophages induce EMT to promote invasion of lung cancer cells through the IL-6-mediated COX-2/PGE2/β-catenin signalling pathway

作者：Che, Dehai; Zhang, Shuai; Jing, Zihan; Shang, Lihua; Jin, Shi; Liu, Fang; Shen, Jing; Li, Yue; Hu, Jing; Meng, Qingwei^*; Yu, Yan^*

来源：Molecular Immunology, 2017, 90: 197-210.

DOI：10.1016/j.molimm.2017.06.018

• Macrophages
• EMT
• NSCLC
• IL-6
• COX-2/PGE2
• beta-catenin

Infiltration of macrophages plays a critical role in the connection between inflammation and cancer invasion; however, the molecular mechanism that enables this crosstalk remains unclear. This paper investigates a molecular link between infiltration of macrophages and metastasis of lung cancer cells. @@@ In this study, the macrophage density and cyclooxygenase-2 (COX-2) protein were examined in surgical specimens by immunohistochemistry (IIIC), and the prostaglandin E2 (PGE2) levels were determined in the blood of 30 non-small cell lung cancer (NSCLC) patients using enzyme-linked immunosorbent assay (ELISA). We demonstrated that macrophage infiltration was significantly associated with elevated tumour COX-2 expression and serum PGE2 levels in NSCLC patients. Interestingly, the COX-2 and PGE2 levels as well as macrophages were poor predictors of NSCLC patient survival. THP-1-derived macrophages were co-cultured in vitro with A549 and H1299 lung cancer cells. In the co-culture process, interleukin-6 (IL-6) induced the COX-2/PGE2 pathway in lung cancer cells, which subsequently promoted A-catenin translocation from the cytoplasm to the nucleus, resulting in epithelial-mesenchymal transition (EMT) and lung cancer cell invasion. @@@ Our findings show that the IL-6-dependent COX-2/PGE2 pathway induces EMT to promote invasion of tumour cells through beta-catenin activation during the interaction between macrophages and lung cancer cells, which suggests that inhibition of COX-2/PGE2 or macrophages has the potential to suppress metastasis of lung cancer cells.

• 出版日期2017-10
• 单位哈尔滨医科大学